Interactions of prostanoids with the platelet activating factors

Mentz, P; Mentz, Graciela; Giessler, C; Mest, H.‐J.

doi:10.1016/0952-3278(92)90179-m

Cited by 10 publications

(2 citation statements)

References 22 publications

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“…PGF 2␣ has diverse physiological actions, ranging from being a potent luteolytic agent (2) to causing vascular smooth muscle contraction (3). In the myocardium, the formation of PGs is induced by pressure overload (4) which can result in cardiac hypertrophy (5,6). Conversely, PG synthase inhibitors diminish the hypertrophic response induced by hypertension (7).…”

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confidence: 99%

Prostaglandin F2α (PGF2α) and the Isoprostane, 8,12-iso-Isoprostane F2α-III, Induce Cardiomyocyte Hypertrophy

Kunapuli¹,

Lawson²,

Rokach³

et al. 1998

Journal of Biological Chemistry

119

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Prostaglandin receptors may be activated by their cognate ligand or by free radical catalyzed isoprostanes, products of arachidonic acid peroxidation. For example, prostaglandin F 2␣ (PGF 2␣ ) causes hypertrophy of neonatal rat ventricular myocytes, via the PGF 2␣ receptor (FP). However, the FP may also be activated by the isoprostane, 8,12-iso-iPF 2␣ -III (Kunapuli, P., Lawson, J. A., Rokach, J., and FitzGerald, G. A. (1997) J. Biol. Chem. 272, 27147-27154). Both ligands induce myocyte hypertrophy with overlapping potencies. Interestingly, the hypertrophic effects of these two agonists on cardiomyocytes are additive. Furthermore, the preference of these two agonists for activation of intracellular signal transduction pathways differs in several respects. Thus, PGF 2␣ and 8,12-isoiPF 2␣ -III stimulate inositol phosphate formation with EC 50 values of 50 ؎ 12 nM and 3.5 ؎ 0.6 M, respectively. Moreover, PGF 2␣ causes a robust activation (ϳ50-fold) of Erk2, whereas 8,12-iso-iPF 2␣ -III has no effect. Similarly, PGF 2␣ causes translocation of cytosolic phospholipase A 2 and also results in a 7-fold increment in the formation of 6-keto-PGF 1␣ , whereas 8,12-iso-iPF 2␣ -III exerts no effect on this pathway. On the other hand, both agonists are equally potent in activating JNK1 and c-Jun, whereas neither activates the p38 kinase. Both PGF 2␣ and 8,12-isoiPF 2␣ -III activate the p70S6 kinase (p70 S6K ), but not Akt, downstream of phosphatidylinositol-3-kinase (PI3K). However, both wortmannin, a PI3K inhibitor, and rapamycin, an inhibitor of p70 S6K activity, inhibit 8,12-isoiPF 2␣ -III -induced myocyte hypertrophy, with IC 50 values of 60 ؎ 12 and 3 ؎ 1.7 nM, respectively, whereas neither compound abrogates the PGF 2␣ -mediated response. Thus, both PGF 2␣ and 8,12-iso-iPF 2␣ -III induce myocyte hypertrophy via discrete signaling pathways. Although both agonists signal via the JNK pathway to initiate changes in c-Jun-dependent gene transcription, PGF 2␣ preferentially activates the MEK-Erk2-cytosolic phospholipase A 2 pathway. In contrast, the PI3K-p70 S6K pathway appears to be essential for 8,12-iso-iPF 2␣ -III-induced myocyte hypertrophy. Prostaglandins (PGs)1 are arachidonic acid metabolites that are produced in a wide variety of tissues in response to mechanical and chemical stimuli. The actions of PGF 2␣ are thought to be mediated via the PGF 2␣ receptor (FP), which is a member of the G protein-coupled receptor (GPCR) superfamily (1). PGF 2␣ has diverse physiological actions, ranging from being a potent luteolytic agent (2) to causing vascular smooth muscle contraction (3). In the myocardium, the formation of PGs is induced by pressure overload (4) which can result in cardiac hypertrophy (5, 6). Conversely, PG synthase inhibitors diminish the hypertrophic response induced by hypertension (7).Prostaglandin F 2␣ (PGF 2␣ ) has recently been shown to stimulate hypertrophy of neonatal rat ventricular myocytes and to induce the expression of myofibrillar genes, independent of muscle contraction (8). Paoni and co-workers (...

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confidence: 99%

Prostaglandin F2α (PGF2α) and the Isoprostane, 8,12-iso-Isoprostane F2α-III, Induce Cardiomyocyte Hypertrophy

Kunapuli¹,

Lawson²,

Rokach³

et al. 1998

Journal of Biological Chemistry

119

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“…The activating effect of PAF on integrins might explain the cardioprotective effect of PAF-antagonists, shown in other studies with coapplication of PMN and platelets [7]. Furthermore, PAF exhibits negative inotropic effects in ischemic and reperfused hearts und vasoconstrictive effects in coronary arteries [19, 20]. …”

Section: Discussionmentioning

confidence: 95%

PMN/Platelets Coinfused in Guinea Pig Hearts Exposed to Low-Flow Ischemia Have no Additive Cardiodepressive Effect

Seligmann

Leitsch²,

Kusus³

et al. 2003

J Vasc Res

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Recent studies revealed an additive cardiodepressive effect of polymorphonuclear granulocytes (PMN) and thrombocytes in hearts exposed to a no-flow ischemia. To find out whether or not this is also true for isolated guinea pig hearts exposed to a low-flow ischemia, the current study was performed. PMN or thrombocytes, together or separately, were applied as a 1-min bolus (1,000/µl or 20,000/µl, respectively) during ischemia or in reperfusion in the presence of thrombin (0.3 U/ml perfusate). Recovery of external heart work and intracoronary cell retention were quantified in percent. Sole application of PMN or platelets during ischemia and reperfusion significantly compromised myocardial function, whereas coapplication of PMN and platelets did not exhibit any further cardiodepressive effect. Coapplication of cells almost prevented intracoronary platelet retention during ischemia and in reperfusion, as opposed to sole platelet application. Known blockers of endogenously released anti-platelet substances like nitric oxide, PGI₂ or adenosine did not mediate a further aggravation of myocardial dysfunction. The platelet-activating factor (PAF) antagonist WEB 2170 BS, however, significantly improved recovery of external heart work during ischemia and in reperfusion. This indicates that an additive cardiodepressive effect of PMN and platelets in working guinea pig hearts exposed to a low-flow ischemia, cannot be demonstrated, whereas PAF antagonists seem to be cardioprotective, under these conditions. Even addition of fibrinogen to the perfusate, did not show an additive cardiodepressive effect of coapplication of PMN and platelets.

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The role of platelet-activating factor in the pathogenesis of gastrointestinal disease

Travis

1994

Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA)

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Interactions of prostanoids with the platelet activating factors

Cited by 10 publications

References 22 publications

Prostaglandin F2α (PGF2α) and the Isoprostane, 8,12-iso-Isoprostane F2α-III, Induce Cardiomyocyte Hypertrophy

Prostaglandin F2α (PGF2α) and the Isoprostane, 8,12-iso-Isoprostane F2α-III, Induce Cardiomyocyte Hypertrophy

PMN/Platelets Coinfused in Guinea Pig Hearts Exposed to Low-Flow Ischemia Have no Additive Cardiodepressive Effect

The role of platelet-activating factor in the pathogenesis of gastrointestinal disease

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